Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029933 | SCV000052588 | pathogenic | Maturity-onset diabetes of the young type 2 | 2023-12-12 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.971T>C (p.Leu324Pro) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246806 control chromosomes (gnomAD). c.971T>C has been reported in the literature in multiple individuals affected with Maturity-Onset Diabetes of the Young (McKinney_2004, Katashima_2021, Mirshahi_2022, Marucci_2023). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15305805, 20005544, 34746319, 36257325, 36227502). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
Athena Diagnostics Inc | RCV003482232 | SCV004229672 | pathogenic | not provided | 2022-12-08 | criteria provided, single submitter | clinical testing | This variant has been identified in multiple unrelated individuals with clinical features of MODY. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |